Cancer Research and Treatment

Original Articles

General

Establishment of Patient-Derived Organoids Using Ascitic or Pleural Fluid from Cancer Patients: Wonyoung Choi, Yun-Hee Kim, Sang Myung Woo, Yebeen Yu, Mi Rim Lee, Woo Jin Lee, Jung Won Chun, Sung Hoon Sim, Heejung Chae, Hyoeun Shim, Keun Seok Lee, Sun-Young Kong; Cancer Res Treat. 2023;55(4):1077-1086. Published online June 12, 2023; DOI: https://doi.org/10.4143/crt.2022.1630

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Purpose
Patient-derived tumor cells can be a powerful resource for studying pathophysiological mechanisms and developing robust strategies for precision medicine. However, establishing organoids from patient-derived cells is challenging because of limited access to tissue specimens. Therefore, we aimed to establish organoids from malignant ascites and pleural effusions.
Materials and Methods
Ascitic or pleural fluid from pancreatic, gastric, and breast cancer patients was collected and concentrated to culture tumor cells ex vivo. Organoids were considered to be successfully cultured when maintained for five or more passages. Immunohistochemical staining was performed to compare the molecular features, and drug sensitivity was assayed to analyze the clinical responses of original patients.
Results
We collected 70 fluid samples from 58 patients (pancreatic cancer, n=39; gastric cancer, n=21; and breast cancer, n=10). The overall success rate was 40%; however, it differed with types of malignancy, with pancreatic, gastric, and breast cancers showing 48.7%, 33.3%, and 20%, respectively. Cytopathological results significantly differed between successful and failed cases (p=0.014). Immunohistochemical staining of breast cancer organoids showed molecular features identical to those of tumor tissues. In drug sensitivity assays, pancreatic cancer organoids recapitulated the clinical responses of the original patients.
Conclusion
Tumor organoids established from malignant ascites or pleural effusion of pancreatic, gastric, and breast cancers reflect the molecular characteristics and drug sensitivity profiles. Our organoid platform could be used as a testbed for patients with pleural and peritoneal metastases to guide precision oncology and drug discovery.

Citations

Citations to this article as recorded by

PRMT1 promotes pancreatic cancer development and resistance to chemotherapy
Bomin Ku, David Eisenbarth, Seonguk Baek, Tae-Keun Jeong, Ju-Gyeong Kang, Daehee Hwang, Myung-Giun Noh, Chan Choi, Sungwoo Choi, Taejun Seol, Hail Kim, Yun-Hee Kim, Sang Myung Woo, Sun-Young Kong, Dae-Sik Lim
Cell Reports Medicine.2024; 5(3): 101461. CrossRef
Establishment and Advancement of Pancreatic Organoids
Dong Hyeon Lee
Keimyung Medical Journal.2024; 43(1): 3. CrossRef
Organoid as a promising tool for primary liver cancer research: a comprehensive review
Xuekai Hu, Jiayun Wei, Pinyan Liu, Qiuxia Zheng, Yue Zhang, Qichen Zhang, Jia Yao, Jingman Ni
Cell & Bioscience.2024;[Epub] CrossRef
The use of organoids in creating immune microenvironments and treating gynecological tumors
Ling-Feng Zhou, Hui-Yan Liao, Yang Han, Yang Zhao
Journal of Translational Medicine.2024;[Epub] CrossRef
Organoid: Bridging the gap between basic research and clinical practice
Guihu Weng, Jinxin Tao, Yueze Liu, Jiangdong Qiu, Dan Su, Ruobing Wang, Wenhao Luo, Taiping Zhang
Cancer Letters.2023; 572: 216353. CrossRef

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Gastrointestinal cancer

Establishing Patient-Derived Cancer Cell Cultures and Xenografts in Biliary Tract Cancer: Jihoon Kang, Ji-Young Lee, Sunmin Lee, Danbee Kim, Jinyeong Lim, Ha Ra Jun, Seyeon Jeon, Young-Ae Kim, Hye Seon Park, Kyu-pyo Kim, Sung-Min Chun, Hee Jin Lee, Changhoon Yoo; Cancer Res Treat. 2023;55(1):219-230. Published online April 6, 2022; DOI: https://doi.org/10.4143/crt.2021.1166

Abstract PDF Supplementary Material PubReader ePub

Purpose
Biliary tract cancers (BTCs) are rare and show a dismal prognosis with limited treatment options. To improve our understanding of these heterogeneous tumors and develop effective therapeutic agents, suitable preclinical models reflecting diverse tumor characteristics are needed. We established and characterized new patient-derived cancer cell cultures and patient-derived xenograft (PDX) models using malignant ascites from five patients with BTC.
Materials and Methods
Five patient-derived cancer cell cultures and three PDX models derived from malignant ascites of five patients with BTC, AMCBTC-01, -02, -03, -04, and -05, were established. To characterize the models histogenetically and confirm whether characteristics of the primary tumor were maintained, targeted sequencing and histopathological comparison between primary tissue and xenograft tumors were performed.
Results
From malignant ascites of five BTC patients, five patient-derived cancer cell cultures (100% success rate), and three PDXs (60% success rate) were established. The morphological characteristics of three primary xenograft tumors were compared with those of matched primary tumors, and they displayed a similar morphology. The mutated genes in samples (models, primary tumor tissue, or both) from more than one patient were TP53 (n=2), KRAS (n=2), and STK11 (n=2). Overall, the pattern of commonly mutated genes in BTC cell cultures was different from that in commercially available BTC cell lines.
Conclusion
We successfully established the patient-derived cancer cell cultures and xenograft models derived from malignant ascites in BTC patients. These models accompanied by different genetic characteristics from commercially available models will help better understand BTC biology.

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Creation and Validation of Patient-Derived Cancer Model Using Peritoneal and Pleural Effusion in Patients with Advanced Ovarian Cancer: An Early Experience
Ruri Nishie, Tomohito Tanaka, Kensuke Hirosuna, Shunsuke Miyamoto, Hikaru Murakami, Hiromitsu Tsuchihashi, Akihiko Toji, Shoko Ueda, Natsuko Morita, Sousuke Hashida, Atsushi Daimon, Shinichi Terada, Hiroshi Maruoka, Hiromi Konishi, Yuhei Kogata, Kohei Tan
Journal of Clinical Medicine.2024; 13(9): 2718. CrossRef

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Clinical Implications of Circulating Tumor DNA from Ascites and Serial Plasma in Ovarian Cancer: Mi-Ryung Han, Sug Hyung Lee, Jung Yoon Park, Hyosun Hong, Jung Yoon Ho, Soo Young Hur, Youn Jin Choi; Cancer Res Treat. 2020;52(3):779-788. Published online February 28, 2020; DOI: https://doi.org/10.4143/crt.2019.700

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to identify the clinical utility of circulating tumor DNA (ctDNA) from ascites and serial plasma samples from epithelial ovarian cancer (EOC) patients.
Materials and Methods
Using targeted next-generation sequencing, we analyzed a total of 55 EOC samples including ctDNA from ascites and serial plasma and gDNA from tumor tissues. Tumor tissues and ascites were collected during debulking surgeries and plasma samples were collected before and after the surgeries. Because one EOC patient underwent secondary debulking surgery, a total of 11 tumor tissues, 33 plasma samples, and 11 ascites samples were obtained from the 10 patients.
Results
Of the 10 patients, nine (90%) contained somatic mutations in both tumor tissues and ascites ctDNA. This mutational concordance was confirmed through correlation analysis. The mutational concordance between ascites and tumor tissues was valid in recurrent/progressive ovarian cancer. TP53 was the most frequently detected gene with mutations. ctDNA from serial plasma samples identified EOC progression/recurrence at a similar time or even more rapidly than cancer antigen 125, an established serum protein tumor marker for EOC.
Conclusion
Our data suggest that ascites ctDNA can be used to identify the mutational landscape of ovarian cancer for therapeutic strategy planning.

Citations

Citations to this article as recorded by

Extensive mutational ctDNA profiles reflect High-grade serous cancer tumors and reveal emerging mutations at recurrence
Giovanni Marchi, Anna Rajavuori, Mai T.N. Nguyen, Kaisa Huhtinen, Sinikka Oksa, Sakari Hietanen, Sampsa Hautaniemi, Johanna Hynninen, Jaana Oikkonen
Translational Oncology.2024; 39: 101814. CrossRef
Current Applications and Challenges of Next-Generation Sequencing in Plasma Circulating Tumour DNA of Ovarian Cancer
Ricardo Roque, Ilda Patrícia Ribeiro, Margarida Figueiredo-Dias, Charlie Gourley, Isabel Marques Carreira
Biology.2024; 13(2): 88. CrossRef
Serial Circulating Tumor DNA Analysis with a Tumor-Naïve Next-Generation Sequencing Panel Detects Minimal Residual Disease and Predicts Outcome in Ovarian Cancer
Jinho Heo, Yoo-Na Kim, Saeam Shin, Kyunglim Lee, Ji-Hyun Lee, Yong Jae Lee, Zisun Choi, Jihyang Park, Seungki Min, Sang Wun Kim, Jong Rak Choi, Sunghoon Kim, Seung-Tae Lee, Jung-Yun Lee
Cancer Research.2024; 84(3): 468. CrossRef
Liquid biopsy into the clinics: Current evidence and future perspectives
Myrto Boukovala, C. Benedikt Westphalen, Victoria Probst
The Journal of Liquid Biopsy.2024; 4: 100146. CrossRef
Cell-free DNA in plasma and ascites as a biomarker of bevacizumab response- a translational research sub-study of the REZOLVE (ANZGOG-1101) clinical trial
Bonnita Werner, Katrin M Sjoquist, David Espinoza, Sonia Yip, Garry Chang, Michelle M Cummins, Linda Mileshkin, Sumitra Ananda, Catherine Shannon, Michael Friedlander, Kristina Warton, Caroline E. Ford
Translational Oncology.2024; 43: 101914. CrossRef
Clinical relevance of circulating tumor DNA in ovarian cancer: current issues and future opportunities
Elena Trevisi, Cristiana Sessa, Ilaria Colombo
Exploration of Targeted Anti-tumor Therapy.2024; 5(3): 627. CrossRef
Cell‐free DNA from ascites identifies clinically relevant variants and tumour evolution in patients with advanced ovarian cancer
Bonnita Werner, Elyse Powell, Jennifer Duggan, Marilisa Cortesi, Yeh Chen Lee, Vivek Arora, Ramanand Athavale, Michael Dean, Kristina Warton, Caroline E. Ford
Molecular Oncology.2024; 18(11): 2668. CrossRef
Phenotyping Tumor Heterogeneity through Proteogenomics: Study Models and Challenges
Diletta Piana, Federica Iavarone, Elisa De Paolis, Gennaro Daniele, Federico Parisella, Angelo Minucci, Viviana Greco, Andrea Urbani
International Journal of Molecular Sciences.2024; 25(16): 8830. CrossRef
Biomarkers in high grade serous ovarian cancer
Mark Bates, Bashir M. Mohamed, Faye Lewis, Sharon O’Toole, John J. O’Leary
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer.2024; 1879(6): 189224. CrossRef
Malignant ascites in pancreatic cancer: Pathophysiology, diagnosis, molecular characterization, and therapeutic strategies
Margaret Y. Han, Erkut H. Borazanci
Frontiers in Oncology.2023;[Epub] CrossRef
Clinical application of liquid biopsy based on circulating tumor DNA in non-small cell lung cancer
Liu Xin, Yang Yue, Ren Zihan, Cui Youbin, Lu Tianyu, Wang Rui
Frontiers in Physiology.2023;[Epub] CrossRef
Advances in application of circulating tumor DNA in ovarian cancer
Ting Xia, Chenyan Fang, Yaqing Chen
Functional & Integrative Genomics.2023;[Epub] CrossRef
Minimal residual disease in solid tumors: an overview
Yarui Ma, Jingbo Gan, Yinlei Bai, Dandan Cao, Yuchen Jiao
Frontiers of Medicine.2023; 17(4): 649. CrossRef
The prognostic impact of peritoneal tumour DNA in gastrointestinal and gynaecological malignancies: a systematic review
Zexi Allan, Sasha Witts, Jeanne Tie, Niall Tebbutt, Nicholas J. Clemons, David S. Liu
British Journal of Cancer.2023; 129(11): 1717. CrossRef
Homologous recombination deficiency (HRD) testing on cell-free tumor DNA from peritoneal fluid
Cyril Roussel-Simonin, Felix Blanc-Durand, Roseline Tang, Damien Vasseur, Audrey Le Formal, Laure Chardin, Elisa Yaniz, Sébastien Gouy, Amandine Maulard, Stéphanie Scherier, Claire Sanson, Ludovic Lacroix, Sophie Cotteret, Lea Mauny, François Zaccarini, E
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Ascites and Serial Plasma Circulating Tumor DNA for Predicting the Effectiveness of Hyperthermic Intraperitoneal Chemotherapy in Patients With Peritoneal Carcinomatosis
Xiaolin Pu, Zongyuan Li, Xiaoying Wang, Hua Jiang
Frontiers in Oncology.2022;[Epub] CrossRef
Transcending Blood—Opportunities for Alternate Liquid Biopsies in Oncology
Bonnita Werner, Kristina Warton, Caroline E. Ford
Cancers.2022; 14(5): 1309. CrossRef
Potential clinical utility of liquid biopsies in ovarian cancer
Jie Wei Zhu, Parsa Charkhchi, Mohammad R. Akbari
Molecular Cancer.2022;[Epub] CrossRef
Whole-Exome Sequencing Reveals Clinical Potential of Circulating Tumor DNA from Peritoneal Fluid and Plasma in Endometrial Cancer
Hye-Yeon Ju, Jung Yoon Ho, Jun Kang, Soo Young Hur, Sejin Kim, Youn Jin Choi, Mi-Ryung Han
Cancers.2022; 14(10): 2506. CrossRef
Circulating tumour DNA — looking beyond the blood
Ann Tivey, Matt Church, Dominic Rothwell, Caroline Dive, Natalie Cook
Nature Reviews Clinical Oncology.2022; 19(9): 600. CrossRef
Mutation analysis of circulating tumor DNA and paired ascites and tumor tissues in ovarian cancer
Xiaoxiang Jie, Ming Du, Meng Zhang, Xiayu Jin, Qingqing Cai, Congjian Xu, Xiaoyan Zhang
Experimental and Therapeutic Medicine.2022;[Epub] CrossRef
Liquid biopsy: current technology and clinical applications
Mina Nikanjam, Shumei Kato, Razelle Kurzrock
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Circulating Tumor DNA—A Novel Biomarker of Tumor Progression and Its Favorable Detection Techniques
Xiaosha Wen, Huijie Pu, Quan Liu, Zifen Guo, Dixian Luo
Cancers.2022; 14(24): 6025. CrossRef
Epithelial ovarian cancer and the use of circulating tumor DNA: A systematic review
Christine Fribert Thusgaard, Malene Korsholm, Kristina Magaard Koldby, Torben A. Kruse, Mads Thomassen, Kirsten Marie Jochumsen
Gynecologic Oncology.2021; 161(3): 884. CrossRef
Cell-free DNA is abundant in ascites and represents a liquid biopsy of ovarian cancer
Bonnita Werner, Nicole Yuwono, Jennifer Duggan, Dongli Liu, Catherine David, Sivatharsny Srirangan, Pamela Provan, Anna DeFazio, Vivek Arora, Rhonda Farrell, Yeh Chen Lee, Kristina Warton, Caroline Ford
Gynecologic Oncology.2021; 162(3): 720. CrossRef
Prediction of the treatment response in ovarian cancer: a ctDNA approach
Mina Sharbatoghli, Somayeh Vafaei, Hamidreza Aboulkheyr Es, Mohsen Asadi-Lari, Mehdi Totonchi, Zahra Madjd
Journal of Ovarian Research.2020;[Epub] CrossRef

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The Effective Use Chlorophyll Derivatives ( CpD ) in Photodynamic Therapy of Ascites Tumors in Mice: Young Joon Park, Won Young Lee, Bo Sup Hahn, Man Jeong Hahn, Jae Kyung Roh, Byung Soo Kim; J Korean Cancer Assoc. 1989;21(1):1-7.

Abstract PDF: A murine ascites tumor was treated with intraperitoneal chlorophyll derivatives (CpD), which were developed as a new photosensitizer in Korea, and light of an appropriate wavelength (670nm). Photodynamic therapy (PDT) was given 3 times at 24h, 48h, and 72h after injection of CpD intraperitoneally. When the PDT was started at 1 week after inoculation of S-180 tumor cells, 80% of the complete remission(clinical) ratewas obtained. When the PDT was started at the 14th day or at the 21st day, the complete remission (clinical) rate was 30% or 0% respectively. This suggested that the lesser the tumor burden was, the higher the complete remission rate was. Our results illustrate the effective use of CpD in photodynamic therapy for the treatment of ascites tumors and reveal the possibility for photodynamic therapy in human ascites tumors.

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Lack of Modifying Effect of Germanium in Rat Hepatic Foci Initiated by Diethylnitrosamine Followed by D - Galactosamine Treatment: Ja June Jang, Sun Ju Lee, Kyung Ja Cho, Sung Ho Kim; J Korean Cancer Assoc. 1989;21(1):7-11.

Abstract PDF: The modification potentials of germanium on the development of preneoplastic hepatic enzyme altered foci were examined in an in vivo midterm assay system. Two week after the initial single ip dose(200 mg/kg) of diethylnitrosamine (DEN), administration of germanium at a concentration of 0.05% on the diet was commenced simultaneously with an ip injection of D-galactosamine at a dose of 300 mg/kg body wt. A11 rats were subjected to two thirds partial hepatectomy at week 5 and sacrificed for assessment of lesion yield at week 8. The modifying potential was scored by comparing the number and area per cm* of induced glutathione S-transferase placental farm-positive (GST-P) foci in the liver with those of the corresponding control group given DEN alone. Germanium showed no statistically significant increase in the number, area and mean diameter of GST-P+ foci.

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Clinical Comparison With Drug Sensitivities by the Human Tumor Colonogenic Assay: Sang Hee Kim; J Korean Cancer Assoc. 1989;21(1):11-18.

Abstract PDF: We tested the ability of the in vitro humman tumor clonogenic assay (HTCA) to predict clinical response for patients with salid tumors. Patients had objectively measurable disease and received three or more courses of single or combination chemotherapy directed by HTCA results. The correlation between clinical responses and in vitro sensitivity was evaluated in 57 patients. Tumor types included breast cancer (25 cases), colon cancer (23 cases) and primary unknown adenocarcinoma (9 cases). In these 57 comparisons, overall predictive accuracy of HTCA for clinical sensitivity was 93%, predictive accuracy for resistance was 97%. Our results suggest that in vitro selection of effective drugs may avoid unnecessary toxicity while assuring therapeutic effects in palliative and adjuvant chemotherapy for the treatment of colon, breast and primary unknown adenocarcinoma.

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